On July 27, 2018 Coherus BioSciences, Inc. (Nasdaq:CHRS), reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the marketing authorization of UDENYCA (formerly CHS-1701), a pegfilgrastim (Neulasta1) biosimilar candidate (Press release, Coherus Biosciences, JUL 27, 2018, View Source [SID1234531701]). UDENYCA has the opportunity to become one of the first pegfilgrastim biosimilars to gain Marketing Authorization in Europe.

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"The positive opinion issued by the CHMP today is a significant milestone for Coherus, as it validates both our UDENYCA biosimilarity package as well as our development platform as a whole," said Denny Lanfear, President and CEO of Coherus BioSciences. "We believe UDENYCA will represent an important option for patients, providers and payers seeking alternatives for the treatment and prevention of febrile neutropenia due to cytotoxic chemotherapy in Europe."

UDENYCA’s marketing authorization application to EMA is supported by analytical similarity data, a 3-arm, triple-crossover pharmacokinetic (PK) and pharmacodynamics (PD) study in healthy subjects, as well as a robust immunogenicity package including a dedicated immunogenicity study in over 300 subjects.

"UDENYCA is clinically differentiated with positive PK/PD and immunogenicity studies in over 600 healthy subjects," said Barbara Finck, M.D., Chief Medical Officer of Coherus BioSciences. "We have worked in a harmonized fashion with the EU and U.S. regulatory authorities, and continue to work with the FDA toward our expected November action date."

The European Commission decision on the approval for UDENYCA is expected in October. UDENYCA is currently under evaluation by the U.S. Federal Drug Administration (FDA) with an action date expected on or before November 3, 2018.

1 Neulasta is a registered trademark of Amgen Inc.

About UDENYCA
UDENYCA, formerly CHS-1701, is a biosimilar candidate to pegfilgrastim, a growth-colony-stimulating-factor (G-CSF) designed to decrease the chance of infection as manifested by febrile neutropenia (fever, often with other signs of infection, associated with an abnormally low number of infection-fighting white blood cells), in patients with non-myeloid (non-bone marrow) cancer who are receiving myelosuppressive chemotherapy that has a clinically significant incidence of febrile neutropenia. Pegfilgrastim is one of the largest selling oncology biologics with worldwide revenues in excess of $4.5 billion in 2017. UDENYCA drug substance manufacturing is located in Boulder, Colorado.

On July 27, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported a Hong Kong initial public offering and a global offering (the "Offering") of 65,600,000 of its ordinary shares, par value $0.0001 per share (the "Shares"), and the proposed listing of the Shares on the Main Board of The Stock Exchange of Hong Kong Limited (the "SEHK") (Press release, BeiGene, JUL 27, 2018, View Source [SID1234528781]). BeiGene’s American Depositary Shares ("ADS") are currently listed on the Nasdaq Global Select Market under the symbol "BGNE." Each ADS represents the right to receive 13 ordinary shares.

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The Offering initially comprises 5,904,000 Shares for subscription by the public in Hong Kong and 59,696,000 Shares for subscription globally, representing 9% and 91% of the total number of Shares, respectively, subject to reallocation. In addition, BeiGene expects to grant the joint global coordinators a 30-day option to purchase up to an additional 9,840,000 Shares. The Offering is subject to market and other conditions, and there can be no assurance as to whether or when the Offering may be completed, or as to the actual size or terms of the Offering.

Morgan Stanley & Co. International plc, Goldman Sachs (Asia) L.L.C., Credit Suisse (Hong Kong) Limited and CLSA Limited are acting as joint global coordinators for the Offering.

Sales of Shares outside of Hong Kong, initially offered in the United States and sold outside the United States that may be resold from time to time in the United States, are being offered pursuant to an automatically effective shelf registration statement that was previously filed with the U.S. Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement relating to and describing the terms of the Offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to these securities may also be obtained for free from the offices of Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014; and Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, or email:[email protected]; and Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, One Madison Avenue, New York, New York 10010, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such state or jurisdiction.

LabCorp has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, LabCorp, 2018, JUL 27, 2018, View Source [SID1234527935]).

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On July 27, 2018 Pierre Fabre reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) in combination for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation (Press release, Pierre Fabre, JUL 27, 2018, View Source [SID1234527945]). This opinion is based on data from the Phase 3 COLUMBUS trial.1 The CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). The decision will be applicable to all 28 EU member states plus Liechtenstein, Iceland and Norway.

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"We are delighted to be one step closer to bringing BRAFTOVI and MEKTOVI to patients with advanced BRAF-mutant melanoma in Europe," said Frédéric Duchesne, President & CEO of the Pierre Fabre Pharmaceuticals Division. "If the European Commission approves BRAFTOVI and MEKTOVI, this will be a new treatment option for these patients who currently have a challenging prognosis."

The CHMP positive opinion is based on results from the Phase 3 COLUMBUS trial, which demonstrated that the combination improved median progression-free survival (PFS), compared with vemurafenib alone (14.9 months versus 7.3 months, respectively: hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41–0.71; p<0.0001).1 As presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2018, treatment with BRAFTOVI and MEKTOVI achieved a median overall survival (OS) of 33.6 months, compared with 16.9 months for patients treated with vemurafenib as a monotherapy (HR 0.61, 95% CI, 0.47–0.79; p<0.0001) in the planned analysis of OS in the COLUMBUS trial.2 Adverse events leading to discontinuation that were suspected to be related to the study treatment occurred in 6% of patients.1 The most common Grade 3–4 adverse events, seen in more than 5% of patients, were: increased gamma-glutamyltransferase (9%), increased creatine phosphokinase (7%) and hypertension (6%).1

Important safety information and recommendations for the use of BRAFTOVI and MEKTOVI will be detailed in the summary of product characteristics (SmPC), which will be published in the European Public Assessment Report (EPAR) and made available in all official EU languages if marketing authorisation is granted by the EC.

On 27 June 2018, Pierre Fabre’s partner Array BioPharma, which has exclusive rights for these medicines in the United States (US), announced that BRAFTOVI and MEKTOVI were approved by the Food and Drug Administration (FDA) in the US for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.3,4 BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma. BRAFTOVI and MEKTOVI are investigational medicines and are not currently approved in any other country outside of the US. Applications for marketing authorisation for BRAFTOVI and MEKTOVI in other countries are currently under review.

About BRAF-mutant Metastatic Melanoma

Melanoma develops when unrepaired DNA damage to skin cells triggers mutations that may lead them to multiply and form malignant tumours. Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates.5,6 There are a variety of gene mutations that can lead to metastatic melanoma. The most common genetic mutation in metastatic melanoma is BRAF. There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma.6–9

About BRAFTOVI (encorafenib) and MEKTOVI (binimetinib)

BRAFTOVI (encorafenib) is an oral small-molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral small-molecule MEK inhibitor which targets key enzymes in the MAPK signalling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma, colorectal cancer, non-small-cell lung cancer, thyroid and others.

Pierre Fabre has exclusive rights to develop and commercialise BRAFTOVI and MEKTOVI worldwide, except in the US and Canada, where Array BioPharma retains exclusive rights; Israel, where Medison has exclusive rights; and in Japan and South Korea, where Ono Pharmaceutical has exclusive rights to commercialise both products.

About COLUMBUS

The COLUMBUS trial (NCT01909453) is a two-part, international, randomised, open-label, Phase 3 trial evaluating the efficacy and safety of BRAFTOVI (encorafenib) in combination with MEKTOVI (binimetinib) compared with vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation.1 All secondary efficacy analyses, including OS, are descriptive in nature. More than 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the COLUMBUS trial.

The CHMP positive opinion is based on results from the Phase 3 COLUMBUS trial, which demonstrated that the combination improved median PFS, compared with vemurafenib alone (14.9 months versus 7.3 months, respectively: HR 0.54, 95% CI, 0.41–0.71; p<0.0001).1 As presented at ASCO (Free ASCO Whitepaper) in June 2018, treatment with BRAFTOVI and MEKTOVI achieved a median OS of 33.6 months, compared with 16.9 months for patients treated with vemurafenib as a monotherapy (HR 0.61, 95% CI, 0.47–0.79; p<0.0001) in the planned analysis of OS in the COLUMBUS trial.2 Adverse events leading to discontinuation that were suspected to be related to the study treatment occurred in 6% of patients.1 The most common Grade 3–4 adverse events, seen in more than 5% of patients, were: increased gamma-glutamyltransferase (9%), increased creatine phosphokinase (7%) and hypertension (6%).1

On July 27, 2018 Siamab Therapeutics, Inc., a biopharmaceutical company developing novel glycan-targeted cancer therapeutics, reported the publication of positive preclinical data for its ST1 antibody drug conjugate (ADC) in multiple models of ovarian cancer (Press release, Siamab Therapeutics, JUL 27, 2018, View Source [SID1234527944]). Siamab’s lead ST1 program targets Sialyl-Tn (STn), a tumor-associated carbohydrate antigen (TACA), which is expressed on ovarian and other solid tumors and is associated with metastatic disease, poor prognosis, chemo-resistance, and reduced overall survival. The paper describes study data demonstrating that Siamab’s humanized anti-STn ADC provides a novel glycan-specific targeting mechanism for the potential treatment of ovarian carcinoma. The data were published online in the peer-reviewed journal PLOS ONE.

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"The published data continue to validate the potential for a STn-targeted therapy in treating ovarian cancer, which today has limited effective treatment options and poor long-term survival," said Jeff Behrens, president and chief executive officer of Siamab. "Our growing body of preclinical evidence with the ST1 program highlights a strong activity profile across a range of ovarian cancer models."

Bo Rueda, Ph.D., director of The Vincent Center for Reproductive Biology at Massachusetts General Hospital, and the principal investigator of studies described in the paper said, "This new paper includes important recent murine patient derived xenograft (PDX) findings that show that the compound is both effective in multiple PDX models and well-tolerated with no target-related toxicities. The known specificity of STn for malignant tissue in combination with the high affinity and STn-specific selectivity of the humanized ST1 antibody therapeutic provide a compelling rationale to evaluate ST1-ADC in patients with STn-expressing ovarian tumors."

In the paper titled, "Humanized anti-sialyl-Tn antibodies for the treatment of ovarian carcinoma," Siamab researchers and collaborators report findings that show Siamab’s humanized anti-STn ADC demonstrated in vitro cytotoxicity specific to STn-expressing ovarian cancer cell lines and inhibited tumor growth in vivo in both cell line- and PDX ovarian cancer mouse models. No significant weight loss or other gross clinical changes were observed for any of the treatment groups in these models, indicating the therapy was well tolerated by all groups.

The paper also describes additional data from a pilot toxicity study in nonhuman primates (NHP) that demonstrates that Siamab’s humanized anti-STn ADC has a favorable safety and pharmacokinetic profile. There were only mild monomethyl auristatin E (MMAE)-class related hematological effects with none being attributed to the targeting of STn. Dose concentrations in the NHP toxicity study were 12 times higher than concentrations used in preclinical mouse models where anti-tumor activity was observed. No weight loss or deaths occurred in the pilot toxicity study. A histopathology review of all major organs showed no observations linked to STn target-associated toxicity.

Ovarian cancer is the most deadly gynecologic cancer in the United States. Despite surgical debulking and chemotherapy, the five-year survival rate remains below 50%. Ovarian cancer has few common targetable mutations, amplifications and/or deletions. The identification of additional alterations in ovarian cancer is key to developing effective, targeted therapies.

Glycosylation of proteins is one of the most abundant and diverse post-translational modifications, with more than half of all human proteins estimated to be glycosylated.1 Targeting an altered glycosylation pattern specific to tumor cells may offer significant anti-cancer benefit.

STn is expressed on a significant number of ovarian cancers, including the well-known ovarian cancer biomarkers CA-125 (MUC16) and MUC1, and is rarely present on normal tissue, which makes it a favorable target for therapeutic intervention in ovarian cancer.2,3 Elevated serum levels of STn occur in the majority of ovarian cancer patients and correlate with lower progression-free survival and overall five-year survival rates.4